III. HUMAN GENE TRANSFER PROPOSAL (tabs 1332/11, 1333, 1337): 
Dr. Walters circulated a chronology of the review process for the 
human gene transfer proposal submitted by Dr. W. French Anderson 
of the National Heart, Lung, and Blood Institute (NHLBI), 
Dr. Steven Rosenberg of the National Cancer Institutes (NCI), and 
Dr. Michael Blaese of NCI. He said the Human Gene Therapy 
Subcommittee of the RAC met on July 29, 1988, to consider the 
first human gene transfer proposal. He noted that this was the 
culmination of a long process that began in 1982 with the 
Presidential Commission on Bioethics report entitled "Splicing 
Life," which noted there was no current national review mechanism 
for considering such proposals. In 1983, the RAC began a process 
of developing such a review mechanism which has come to consist 
of three parts: review at the local level by local Institutional 
Review Boards (IRBs) for human subjects research and the local 
Institutional Biosafety Committee (IBC); mid-level review by the 
Human Gene Therapy Subcommittee and the RAC; and the final review 
by the NIH Director who accepts or rejects the recommendations of 
the RAC. 
While the Human Gene Therapy Subcommittee was formed in 1983, it 
wasn’t until 1987 that it was asked to examine a preliminary 
draft proposal. Dr. French Anderson, along with his colleagues, 
produced a state-of-the-art review of human gene therapy that 
dealt primarily with a genetic enzyme deficiency disorder, 
adenosine deaminase (ADA) deficiency, as a model for human gene 
therapy. Though never formally submitted as a clinical proposal, 
it did allow the Human Gene Therapy Subcommittee an opportunity 
to study the scientific literature, to become familiar with the 
technical and ethical issues surrounding gene therapy, and to 
receive comments from outside consultants. 
In June 1988, the first clinical protocol involving gene transfer 
into humans was submitted to the local review bodies at NIH. The 
experiment dealt not with ADA deficiency, but with cancer, and 
was not a proposed treatment, but a diagnostic technique. 
Dr. Walters presented a scientific summary of the protocol 
submitted: 
"Tumor infiltrating lymphocytes (TIL) would be isolated 
from a patient's tumor and grown in culture in the 
presence of interleukin-2 (IL-2). An aliquot of TIL 
would be removed at the time they reached log phase 
growth. The aliquot (representing no more than one- 
third of the total TIL population) would be incubated 
with the retroviral vector N2 (containing the gene 
coding for neomycin resistance, or Neo") . This treated 
Recombinant DNA Research, Volume 13 
[233] 
